The goal of this proposal is to elucidate the pathogenesis of Kaposi sarcoma (KS) in the presence or absence of IEV infection, based on the hypothesis that glucocorticoids and certain cytokines/monokines (IL-l, TNF, IL-6, novel growth factors) act directly and indirectly to induce and enhance the growth of KS. A case-control study will be employed for HIV-related KS among homosexual men with a relatively intact immune system (CD4),200/dl, no AMS-defining opportunistic infections). Cases will be accrued from the KS clinics at the LAC/USC Medical Center (N=160). Three age-matched controls will be identified per case. Group I controls will be EIV-positive clinically asymptomatic homosexual friend controls; Group 2 controls will be HIV-negative homosexual friend controls; Group 3 controls will be HIV-negative heterosexual neighborhood controls. Classic KS cases will be identified from the Los Angeles County population based cancer registry (CSP) (n=272). Controls for these cases will be age-matched neighborhood controls identified using a predetermined algorithm. An epidemiologic questionnaire, blood and urine specimens will be obtained on all participants. In addition KS tissue will be obtained on all A.MS-KS cases and on a sample of clinic KS cases. We will determine (1) if plasma ACTH, serum cortisol and urinary free cortisol are elevated in KS cases compared to controls; (2) if serum and short term blood monocyte/macrophage culture supernatant cytokine/monokine levels (TNF, EL-1, EL-6) and urinary IL-6 levels are present at higher levels in cases compared to controls; (3) if certain epidemiologic characteristics are KS risk factors, such as use of steroids, history of certain sexually transmitted diseases, indices of altered immune function, etc. A secondary objective of the proposal is to establish a serum and tissue bank for use in future studies.